The physiological function and the mode of regulation of the transglutaminases which catalyze the formation of covalent cross-links between protein molecules are being studied. Three distinct classes of these enzymes participate in stabilization of the fibrin clot and in cross-linking of other proteins. The roles of individual transglutaminases in formation of cellular membranes and in the membrane-mediated stimulation of specific cellular function, and the regulation of tissue matrix stabilization following injury by the release and generation of active transglutaminase from the cells involved in wound healing are under investigation. The ameobocytes of Limulus Polyphemus show cellular properties similar to human plateletes in their ability to adhere, to aggregate, and to release cellular transglutaminase for formation of a matrix of protein polymers at the site of injury. Thus this system was chosen to serve as a model to study the complex wound healing process. Since cold-insoluble globulin is known to play a role in cell attachment, this protein is being characterized.